D3 – Jeff T Bowles

The 48 Genes that Shape Aging: A Deep Exploration of Horvath’s Universal Mammalian Aging System

February 2, 2025 jefftbowles

I had AI do a quick summary of a very comprehensive deep dive study of Horvath’s 48 aging related genes from the first preprint of his seminal paper Universal DNA methylation age across mammalian tissues -Nature Aging August 2023- The deep dive will be available in my upcoming book on the subject
here’s what it gave us:

What follows is an overview of Stephen Horvath’s Universal Mammalian Epigenetic Aging system. This updated review:

Clarifies that Thymine DNA Glycosylase (TDG), not TET enzymes, is the primary mechanism preventing hypermethylation of these aging-related genes (TDG is α-ketoglutarate dependent).
Explains that the initial 48 genes come from Horvath’s first preprint, and subsequent revisions have added or changed several genes (including transcription factor SP1).
Highlights how SP1 ties together MAO-A/MAO-B, FAD sequestration, WRN protein expression, and a potential impact on aging processes.
Presents a CD38/NAD+ analysis of the 48 genes, discussing how some of them may influence CD38 activity, thereby modulating NAD+ levels.

Throughout, we underscore the interplay of GABA–α-KG–glutamate, the overrepresentation of splicing-related genes, and the newly emphasized roles of SP1 and MAO in driving epigenetic and metabolic shifts that contribute to aging.

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How to Save 90%+ On Any Supplement!

March 23, 2024 jefftbowles 36 Comments

(Supplements/Hormones Available 90%+ OFF- Vitamin D3, Vitamin K2, DHEA, pregnenolone, melatonin, hyaluronic acid, resveratrol, don’t see it? Just ask). Did…

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Ancient Blueprints of Decline: How Four Evolutionary Waves Over 800 Million Years Shaped the Aging We Know Today

March 22, 2024 jefftbowles

Abstract

What if aging isn’t just a random failure of worn-out cells, but rather a four-layered design embedded in our DNA from the earliest chapters of life on Earth? This article uncovers startling clues that point to a single, ancient partnership between archaea and bacteria—both essentially “immortal” when solitary—as the evolutionary spark that ignited multicellularity, predation, sex, and aging. By tracing life’s major leaps from fermentation-based “plant-like” ancestors to the mitochondrial energy revolution, from advanced DNA-repair machinery to the rise of sexual reproduction with its own master aging regulator (WRN), we find that aging may have emerged in four distinct evolutionary waves. Each wave appears to have etched its own “choke points” into the biology of today’s humans, showing up dramatically in diseases like progeria and Werner’s syndrome.

Beyond a mere historical narrative, these insights offer a powerful lens through which to view—and potentially reverse—the aging process. They also challenge the conventional wisdom that aging is merely wear-and-tear, suggesting instead that it may be at least partly “designed” for a purpose: to keep populations genetically nimble in the face of ever-evolving predators and environments. If you’re an aging researcher or a bold biology professor hungry for revolutionary concepts, this synthesis of cutting-edge evolutionary data and provocative experimental evidence (including a case of a spontaneously imploding rat tumor) promises to make you rethink the very nature of cellular senescence—and how we might learn to outmaneuver it.

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In Simple Terms: Rewinding the Clock: How Young DNA Injections Could Help Turn Back the Hands of Aging

March 21, 2024 jefftbowles

Abstract (Easy to Understand Article)
Imagine if a simple injection of “young DNA” could help older animals—and potentially people—turn back the clock. Scientists now suspect that tiny genetic signals, whether from exosomes (little bubbles with microRNAs) or purified DNA fragments, might push aging cells to act younger. One striking example is Dr. Harold Katcher’s “E5” therapy, which used factors from young pig blood to reverse biological age markers in rats by over 60%. Researchers also note that normal cell turnover (apoptosis) might naturally release small DNA pieces that keep tissues “in sync” with a body’s overall age, suggesting there’s already a built-in system for coordinating youth signals. By carefully harnessing these DNA or RNA-based messengers—and ensuring they don’t trigger harmful immune responses—we could be looking at a new and surprisingly straightforward route to rejuvenation. This paper highlights how epigenetics, exosomes, and possibly even raw DNA injections are coming together in the quest to make cells feel (and function) younger.

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